Because of its large energy requirements as it functions in the visual process, the retina requires a well-functioning vascular system to provide a sufficient, well-regulated blood supply. The ability of the retinal circulation to autoregulate its blood supply in accordance with metabolic needs is central to its proper functioning. An abnormal retinal blood flow rate is an early indicator of retinal vascular pathology. The laser Doppler technique is a clinically applicable, noninvasive technique that enables one to obtain measurements of the blood flow rate at selectable sites in the retinal vasculature. It is the only known noninvasive technique that can provide objective, quantitative measurements of retinal blood flow. In addition, the laser Doppler technique is the only known technique that can measure instantaneous changes in the velocity of red blood cells flowing in individual retinal vessels, a requirement for the complete characterization of retinal hemodynamics. Further improvements in the laser Doppler technique, its application to studies aimed at elucidating the operation of the autoregulatory mechanism, and its application to studies of retinal vascular disease, with emphasis on diagnosis, prognosis, and monitoring the effectiveness of therapeutic interventions, should lead to substantial new information about retinal blood flow and its role in the development of retinal diseases. Accordingly, the specific aims of the proposed research involve (a) continued instrument development with the goal of simplifying and automating the laser Doppler data acquisition and analysis procedures; (b) investigation of the response of the retinal circulation to normal physiologic systemic changes (pregnancy and aging) and to changes in local retinal stimuli; (c) clinical studies of retinal blood flow abnormalities in diabetes and the effects of pharmacologic intervention in diabetes; and (d) the effect of therapeutic intervention in patients with venous occlusive disease or retinal detachment.